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Stephen Hawking's Disease: How ALS Impacts The Body And Progress For Treatment
Key Takeaways on ALS, or Stephen Hawking's Condition:
ALS stands for amyotrophic lateral sclerosis and is also known as Lou Gehrig's disease.
Stephen Hawking lived with ALS for 55 years and advocated for research and helped bring awareness to the disease.
ALS is fatal, and impacts a person's ability to talk, eat, walk, and breath. Progress for treatment includes a genetic treatment, Qalsody, that was approved by the Federal Drug Administration (FDA) in 2023.
In 1939, Lou Gehrig, the first baseman for the New York Yankees, shocked the baseball world when he benched himself mid-season after playing 2,130 consecutive games. Though he'd had a stellar season the year prior, something was different. He didn't know it quite yet, but he was beginning to experience the symptoms of amyotrophic lateral sclerosis (ALS). Doctors diagnosed Gherig on his 36th birthday, and he passed away just before his 38th.
Renowned physicist Stephen Hawking was diagnosed with ALS (also known as Lou Gehrig's disease) in 1963. However, doctors were still unsure what caused the disease and if there were any possible treatments. Hawking's doctors gave him about two years to live, however, he lived with the disease for 55 years.
During his life and career, Hawking was an advocate for ALS research and helped bring awareness to the disease. With his outreach and the help of viral challenges like the Ice Bucket Challenge in 2014, scientists have identified many new genes associated with ALS. There is hope that scientists will one day combat the disease with targeted gene therapies.
What Is ALS?
Schematic illustration of the neuron affected by amyotrophic lateral sclerosis disease, or ALS, a progressive disease of the nervous system that causes loss of muscle control. (Image Credit: ilusmedical/Shutterstock)
When Gehrig announced his retirement, many people learned about ALS for the first time. But scientists a century earlier were making note of a progressive weakness they thought was rooted in a neurogenic cause. Now, researchers better understand the cause of the disease as well as the expected progression.
"ALS is a fatal disease where a person's brain stops communicating with their muscles. This means a person loses the ability to walk, talk, eat, and eventually breathe. It takes a devastating toll on entire families — physically, emotionally, and financially," says Brian Frederick, the Chief Marketing and Communications Officer for The ALS Association.
Stephen Hawking's Condition: The Longest Survivor of ALS
ALS is a rare disease, and only in the past few years did the Centers for Disease Control and Prevention (CDC) create a registry that officially tracked ALS prevalence in the U.S. In 2022, almost 33,000 cases were reported.
Including Gehrig, there have been a few famous people with ALS. World-renowned physicist Stephen Hawking lived with ALS for 55 years. He was diagnosed at age 21 and lived with the disease until 2018. Hawking was the longest living person living with ALS, and the average survival time after diagnosis is three years.
"ALS is always fatal, usually within two to five years of diagnosis. There are some individuals who live much longer with ALS, but we don't know why yet," Frederick says.
Read More: From Thoughts To Words: How AI Deciphers Neural Signals To Help A Man With ALS speak
Advances in ALS Research and Treatment
Superoxide dismutase 1 (SOD1) enzyme. Converts superoxide radical in hydrogen peroxide. Gene mutations cause ALS (amyotrophic lateral sclerosis). (Image Credit: StudioMolekuul/Shutterstock)
For people living with ALS, the progression of the disease can vary. ALS affects motor neurons and creates paralysis in a person's legs and arms. They will also lose control over the muscles that allow them to speak, swallow, and breathe. For some people, the paralysis may begin in their legs. For others, it can start with their voice.
"We have seen several new ALS genes identified, which gives the research community targets for potential therapies," Frederick says.
Researchers were able to develop a targeted therapy for one of the identified genes, the superoxide dismutase 1 (SOD1) gene. A genetic treatment, Qalsody, was approved by the Federal Drug Administration (FDA) in 2023 and then by regulating agencies in the European Union in 2024.
Although the introduction of Qalsody is seen as progress, it can only treat patients with the mutation in the SOD1 gene. Currently, the CDC estimates there are fewer than 500 patients in the U.S. Who have this type of mutation and will benefit from the new drug.
In 1993, SOD1 was the first gene associated with ALS. By the time of the 2014 Ice Bucket Challenge, more than 20 associated genes were known to scientists. Now, more than 40 genes have been identified, which will help scientists work toward target treatments.
Hope for an ALS Cure
Although progress is being made, there is currently no cure for ALS, and advocates hope another surge in public interest could help fund further studies.
"Anyone can get ALS at any time, and it's a brutal disease. People who are diagnosed and their families often express that they prayed for cancer or MS or anything other than ALS before that final diagnosis," Frederick says.
This article is not offering medical advice and should be used for informational purposes only.
Read More: A Soft Ventilator Could Help People with ALS Breathe Easier
Article Sources
Our writers at Discovermagazine.Com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
Emilie Lucchesi has written for some of the country's largest newspapers, including The New York Times, Chicago Tribune and Los Angeles Times. She holds a bachelor's degree in journalism from the University of Missouri and an MA from DePaul University. She also holds a Ph.D. In communication from the University of Illinois-Chicago with an emphasis on media framing, message construction and stigma communication. Emilie has authored three nonfiction books. Her third, A Light in the Dark: Surviving More Than Ted Bundy, releases October 3, 2023, from Chicago Review Press and is co-authored with survivor Kathy Kleiner Rubin.
New Research On ALS Opens Up For Early Treatment
Using the gene scissors CRISPR and stem cells, researchers at Stockholm University and the UK Dementia Research Institute (UK DRI) at King's College London have managed to identify a common denominator for different gene mutations that all cause the neurological disease ALS. The research shows that ALS-linked dysfunction occurs in the energy factories of nerve cells, the mitochondria, before the cells show other signs of disease, which was not previously known. The study was recently published in the scientific journal Nature Communications.
"We show that the nerve cells, termed motor neurons, that will eventually die in ALS have problems soon after they are formed. We saw the earliest sign of problems in the cell's energy factories, the mitochondria*, and also in how they are transported out into the nerve cells' long processes where there is a great need for them and the energy they produce," says Dr Eva Hedlund at Stockholm University, head of the study together with Dr Marc-David Ruepp at the UK Dementia Research Institute at King's College London.
The research team was able to establish that these problems were common to all ALS-caused mutations, which will be important for future treatments of the disease.
"This means that there are common factors that could be targeted with drugs, regardless of the cause of the disease," says Dr Eva Hedlund.
Reprogrammed cells
The researchers used the gene scissors CRISPR/Cas9 to introduce various ALS-causing mutations into human stem cells, called iPS cells*. From these, motor neurons, the nerve cells that are lost in in ALS, and interneurons, nerve cells that are relatively resistant to the disease, were produced. These were then analyzed with single-cell RNA sequencing, a method that enables identification of all messenger molecules (mRNA) in each individual cell and with that understand how a particular cell works, how it talks to its neighbors and if it starts to have problems.
"In the data we obtained, we identified a common disease signature across all ALS-causing mutations, which was unique to motor neurons and thus did not arise in resistant neurons," says Dr Christoph Schweingruber, first author of the study.
This happened very early and was completely independent of whether the disease-causing mutated proteins (FUS, or TDP-43) were in the wrong place in the cell or not.
"Until now, it has been believed that it is the change where the proteins are within the cells, called mislocalization*, that occurs first," says Dr Marc-David Ruepp.
A groundbreaking discovery
In ALS, it is often said that some problems are caused by a loss of function in a protein that is mutated, while other problems arise due to the opposite, namely the emergence of a new toxic function that has been obtained through the mutation, called "gain-of-function," but according to Eva Hedlund, it has not always been easy to clarify how it really works and much is still unknown.
"By making various CRISPR mutations in the ALS-causing FUS-gene*, we have now been able to show for the first time that most errors arising are caused by a new toxic property of the protein, not by a loss of function," says Dr Christoph Schweingruber.
Affecting the cells' energy factories
A third discovery was that the transport of mitochondria out into the axons*, the extensions of the nerve cells where most mitochondria in nerve cells are needed, was radically affected in the ALS lines. This happened independently of whether the disease-causing proteins were in the wrong place in the cell or not.
"A fact that poses a problem because there is a great need for these energy factories in the extensions of the nerve cells. Without them the nerve cells do not have enough energy to communicate properly with other cells," says Dr Eva Hedlund.
The new discoveries open up for early treatment methods, something that for the research team is a continuous work in progress.
"We are trying to understand how these early errors occur in the sensitive motor neurons in ALS, and how it affects energy levels in the cells and their communication and necessary contacts with muscle fibers. We believe that these are important keys to the understanding of why the synapses between motor neurons and muscles is broken in ALS and also to identify new targets for therapies," says Dr Eva Hedlund.
About ALS
The fatal disease ALS is characterized by the death of nerve cells in our brain and spinal cord, so-called motor neurons, which control all our skeletal muscles in the body, and this leads to the breakdown of the muscles. In most cases of ALS, the disease occurs sporadically, but in 10-20 percent of cases, different gene mutations cause the disease. It has so far been unknown whether different mutations cause ALS in the same way. It has also been unknown why some nerve cells are sensitive while others are resistant.
Glossary to ALS research
Q&A: Neurofilament Light Chain Detection May Be Breakthrough In ALS Detection
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Key takeaways:In ALS, a neurodegenerative condition that leads to loss of muscle control and executive function, there is a need for blood-based biomarkers to assist clinicians in early detection and treatment efforts.
Healio spoke with Joshua A. Bornhorst, PhD, from the Mayo Clinic's division of clinical biochemistry and immunology, to learn about the latest in biomarker detection technology and its future implications for patients with ALS.
Healio: Is there a need for rapid testing and diagnosis for ALS?
Bornhorst: As with other neurodegenerative diseases, blood tests are attractive tools to support evaluation of potential cases. Presently, clinical and imaging studies are also involved in establishing diagnosis. Rapid testing (such as in-office testing) is not needed, as the diagnostic process requires careful consideration by a specialist to confirm a diagnosis.
Healio: What factors led to the decision to pursue development of a blood-based biomarker?
Bornhorst: Neurofilament light chain (NfL) has been known as a potential blood-based assay to assess neuronal damage associated with neurodegenerative disorders. As such, it is an attractive target for diagnostic assay manufacturers. NfL testing in plasma has been clinically available for a few years at Mayo Clinic Laboratories, with which I am associated along with Dr. Alicia Algeciras-Schimnich, the co-director of the Clinical Immunoassay Laboratory section.
Healio: What led to the discovery that NfL was not only present in patients with ALS but also had two to three times higher concentration in those unaffected?
Bornhorst: As a nonspecific neuronal damage marker, efforts around the world have been made to evaluate NfL as a potential diagnostic and prognostic disease blood-based marker. Other neurodegenerative diseases for which it has been evaluated, include multiple sclerosis, frontotemporal dementia, Parkinson's, and Alzheimer's disease. While NfL has not been proven to be the most effective blood-based diagnostic marker in a number of these disorders such as AD, in recent work such as a study published in Neurology this past February, researchers showed that NfL remains a diagnostic blood-based frontrunner in regard to ALS at this time.
Healio: How will this new method be tested, and how long would it take before data becomes sufficient to recognize it as a reliable detection source for ALS?
Bornhorst: While effective analytic testing for NfL has been demonstrated, a number of neurological disorders including traumatic brain injury and concussion also elevate NfL. In some studies, such as by Mondesert et. Al. The overall accuracy of NfL blood testing for ALS is about 90%. However, the accuracy of testing may differ in other populations.
Given that numerousother non-ALS related factors can alter NfL concentration, further study needs to be done to establish whether NfL can be considered diagnostic. However, it does not seem to be specific enough to ALS to be potentially diagnostic at this time and likely will need to be used in conjunction with other clinical, imaging and other biomarkers.
Healio: Should the test become standard, how, by whom, and in what settings would it be administered?
Bornhorst: As factors such as age (NfL concentrations increase about 2%- to 3% per year of age), chronic kidney disease, and other clinical factors can increase NfL concentrations, I do not think it will be used at home, or in most primary care offices.
Effective use of NfL will likely require a physician who is well-versed in neurological biomarkers. Specialists such as neurologists have already adopted some use of NfL, and it may gradually spread to other physicians. Widespread use and reimbursement will require increasing comfort with the diagnostic results and the eventual incorporation of NfL testing into professional guidelines/recommendations for use.
Healio: What would early detection for patients via the biomarker test mean for treatment and quality of life in ALS?
Bornhorst: As some treatments can slow the progression of ALS, early detection of the disease and underlying pathology is very valuable. However, the ability of NfL for early diagnosis has not been fully explored. NfL also provides apparent insight into prognosis as well as how quickly the disease might progress. Finally, multiple NfL measurements over time may be able to monitor how current and future treatments are used to adjust treatments. This can make a real difference in the quality of life for the ALS patient.
One can look to the rapid progress in AD diagnosis and treatments over the last few years.
This progress has been hastened by the recent availability of very effective blood marker tests for Alzheimer's such as p-tau217. This demonstrates effective diagnostic testing is a very necessary piece of the puzzle in the creation of treatment advances. Hopefully, this will also be the case for ALS.
Reference:Bornhorst JA, et al. Clin Chim Acta. 2022;doi:10.1016/j.Cca.2022.08.017.
Figdore DJ, et al. J Lab Precis Med 2024; doi:10.21037/jlpm-24-33. [JB1]
Mondesert E, et al. Neurology. 2025;doi:10.1212/WNL.0000000000213400.
For more information:Joshua A. Bornhorst, PhD, can be reached at Bornhorst.Joshua@mayo.Edu.
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